Developmental Trajectories in ARID1B-Related Disorder – a Multi-Method Multi-Site Prospective Natural History Study

ARID1B 相关疾病的发育轨迹 – 多方法、多地点前瞻性自然历史研究

• 批准号: 542554376
• 负责人: Professor Dr. Peter Krawitz
• 金额: --
• 依托单位: Université de Montréal
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/542554376?language=en
• 关键词: Developmental; Trajectories; ARID1B; Related; Disorder

ARID1B is the most frequently mutated single gene among neurodevelopmental disorders (NDDs) that are not inherited, with an approximated prevalence of one in 9,500 individuals. ARID1B-related disorder (ARID1B-RD) manifests in early childhood as moderate to severe developmental delay, and children and adults with the disorder have intellectual disability (ID) and are often diagnosed with autism spectrum disorder along with many other clinical signs. Despite ARID1B-RD’s high prevalence and extensive debilitating effects, the current understanding of how the disorder develops over time is strikingly limited. The proposed project will address this gap by employing a prospective longitudinal multi-method design. Specifically, in six sites, we will monitor the development of 100 children and adolescents aged 2-18 with ARID1B-RD for three years. Monitoring will involve (a) administration of standardized NDD assessments complemented by ARID1B-RD-specific tools; (b) evaluation of biological aspects of ARID1B-RD (for example, electric brain activity); and (c) collection of daily life data via caregivers’ reports, and audio and movement data using smartwatches and microphones. The project team brings a diverse set of complementary skills and collaborates with a leading patient advocacy organization. The project will generate a comprehensive picture of the progression of ARID1B-RD . The data will allow identifying and validating measurable targets for interventions, thus facilitating the development of effective treatments for thousands of children worldwide.

ARID1B是非遗传性神经发育障碍（ndd）中最常发生突变的单基因，患病率约为9500人中有1人。arid1b相关障碍（ARID1B-RD）在儿童早期表现为中度至重度发育迟缓，患有该障碍的儿童和成人患有智力残疾（ID），并且通常被诊断为自闭症谱系障碍以及许多其他临床症状。尽管ARID1B-RD的高患病率和广泛的衰弱效应，但目前对这种疾病如何随着时间的推移而发展的了解非常有限。拟议的项目将通过采用前瞻性纵向多方法设计来解决这一差距。具体而言，我们将在六个地点监测100名2-18岁患有ARID1B-RD的儿童和青少年的发展，为期三年。监测工作将涉及(a)管理标准化的非破坏性疾病评估，辅之以arid1b - rd特定工具；(b)评估ARID1B-RD的生物学方面（例如，脑电活动）；(c)通过护理人员的报告收集日常生活数据，以及使用智能手表和麦克风收集音频和运动数据。项目团队带来了一套多样化的互补技能，并与领先的患者倡导组织合作。该项目将产生ARID1B-RD进展的全面情况。这些数据将有助于确定和验证干预措施的可衡量目标，从而促进为全世界数以千计的儿童开发有效的治疗方法。